We have developed and reported a method for analyzing the diffusing capacity in the nonuniform lung. We are also able to give an estimate for nonuniformities in the distribution of diffusion. The method uses a multi-breath approach which greatly multiplies the available data. During this year we have developed equipment and programs to permit us to apply this relatively sophisticated test of gas exchange to clinical populations. We will specifically study human subjects with antitrypsin deficiency enrolled in a longitudinal study and a patient population from another broader based study of obstructive disease in order to determine the ability of these tests to assess changes in lung function, both in the early stages and as the disease progresses. We will also study the changes in the diffusing capacity in normals with lung volume, exercise and other respiratory maneuvers.